Researchers Create HIV-Resistant Cells in Mice

Scientists from the Keck School of Medicine at the University of Southern California have created HIV-resistant cells from modified blood stem cells. They have used a mouse model to test the cells that target one of two molecules that HIV uses to enter human cells, which one day may help to create less-harsh treatments for the virus.

“The strategy arose from the observation that people with a mutation in a gene called CCR5 are naturally resistant to infection with the most common strains of HIV and do not develop AIDS,” said Meghan Lewit, spokeswoman for the team of researchers.

CCR5 is a protein that helps the HIV virus penetrate a cell. The variant, called CCR5 delta 32, results in smaller CCR5 proteins which prevents most strains of HIV from infecting the cells.

The team used enzymes to knock out the CCR5 gene in human blood stem cells and then transplanted the modified stem cells into mice. The cells developed into mature cells of the human immune system, including the T cells that HIV infects. When the mice were then infected with HIV, the animals were able to maintain normal levels of human T cells and suppress HIV.

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The results are unlike typical research in animals because the mice have been "humanized": They have human immune systems and resisted a human disease.

If the approach can be applied to humans, it could enable a long-term generation of HIV-resistant cells in the body, providing the potential for the patient's cells to suppress HIV, Lewit said.

Paula Cannon, principal investigator and associate professor of molecular microbiology and immunology said, “By engineering CCR5-deficient stem cells, we may allow a patient to produce HIV-resistant cells in all of the cell types that the virus infects, and for long periods of time. We’ve done it at the scale of a mouse, and the challenge now is to see if this can be done at the scale of a human patient.”

Cannon and colleagues would like to begin testing in HIV-positive lymphoma patients who have already had stem cells removed. The treatment would “piggyback” another gene therapy treatment. She suspects that human trials, though, will not begin for at least another four years.

If successful, treatments can be created that would allow patients to control HIV without anti-retroviral drugs, albeit at great expense. Cannon estimates gene therapy of this type to cost $100,000, but if it allows an HIV patient to avoid taking drugs for the rest of their lives, it should be cost-effective over time.

The study was released online July 2 in the journal Nature Biotechnology.

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